Significantprogresshasbeenmadeinunderstandingthedifferentiationofthefiveendocrinecellsoftheparsdistalisfromoneprecursorcell.ThehomeodomaintranscriptionfactorPROP-1 isexpressedsoonafterRathke’spouch(embryologicalprecursoroftheadenohypophysis)formsandpromotesthecelllineagesofsomatotropes,lactotropes,thyrotropes,andgonadotropes.Inhumans,raremutationsinthePROP1 generesultinatypeofcombined pituitary hormone deficiency. TheseindividualsdisplaydwarfismduetolackofGH,cognitivedeficitssecondarytohypothyroidism,andinfertilityduetolackofgonadotropins.Asubsequentlyexpressedpituitary-specifichomeodomaintranscriptionfactorcalledPOU1F1 (formerlyknownasPit-1)isrequiredfordifferentiationofthyrotropes,somatotropes,andlactotropes,anditdirectlystimulatestranscriptionandexpressionofTSH,GH,andprolactin.AffectedindividualswithPOU1F1 mutationshavedwarfismandintellectualdisability.Thenuclearhormonereceptor–relatedtranscriptionfactorsteroidogenic factor-1 (SF-1) wasoriginallyidentifiedintheadrenalcortexandgonadsasaregulatorofsteroidogenicenzymegeneexpression.SF-1isalsoexpressedinGnRHneuronsinthehypothalamusandinpituitarygonadotropes,whereitregulatestranscriptionofLHandFSH.MutationsintheSF1 genedisruptadrenalandgonadalfunction,includinglossofgonadotropesinthepituitarygland.TPIT isatranscriptionfactorinvolvedinthedifferentiationofcorticotropes.TPIT,actingwithothertranscriptionfactors,promotesdifferentiationofcorticotropesandexpressionofthePOMC gene(seeCorticotropessection).MutationsinthehumanTPIT generesultinisolated ACTH deficiency. Thisresultsinaformofsecondary adrenal insufficiency thatrequireslifelongreplacementwithglucocorticoids(see
The hypothalamic regulation of anterior pituitary function is neurohormonal. An area of the hypothalamus collectively referred to as the hypophysiotropic (i.e., stimulatory to the hypophysis) region contains nuclei composed of small, or parvocellular, cell bodies that project axons to the
Transcription, excision, splicing •Fig. 41.4 Synthesisandprocessingofpreprovasopressinorpreprooxytocin.
median eminence. They are distinct from the magnocellular neurons of the PVN and SON that project to the pars nervosa. Parvocellular neurons secrete releasing hormones from their axonal termini at the median eminence (Fig.
41.7 ). The releasing hormones enter a primary plexus of fenestrated capillaries and are then conveyed to a second capillary plexus located in the pars distalis by the hypothalamohypophyseal portal vessels (a portal vessel is defined as a vessel that begins and ends in capillaries without going through the heart). At the secondary capillary plexus, the releasing hormones diffuse out of the vasculature and bind to their cognate receptors on specific cell types within the pars distalis. The neurovascular link (i.e., pituitary stalk) between the hypothalamus and pituitary is somewhat fragile and can be disrupted by physical trauma, surgery, or hypothalamic disease. Damage to the stalk and subsequent functional isolation of the anterior pituitary result in a decline in all anterior pituitary tropic hormones except prolactin (discussed later).